Vitamin A and beta-carotene are potentially useful agents in the prevention of a wide variety of human epithelial type cancers. Chemoprevention trials with both vitamin A and beta-carotene have been designed using doses of these agents selected mainly on an empirical basis. For example, the doses of beta-carotene being used in a variety of ongoing prevention studies vary between 15 mg to less than 100 mg per day. Normal subjects trials to evaluate the plasma, skin and fat levels beta-carotene at low, intermediate and relatively high doses could establish a pharmacologic rationale for future beta-carotene dose selection. Additionally, the evaluation of TPA induced ornithine decarboxylase activity in skin biopsy samples obtained from beta-carotene treated normal subjects could establish a biologic rationale for beta-carotene dose selection. We plan to enter 100 normal subjects into a phase II and pharmacokinetic trial of beta-carotene doses of 0 (placebo), 15, 30, 60 and 120 mg per day for up to two years with plasma, skin and fat concentrations of beta-carotene, retinol and retinyl palmitate and TPA stimulated ODC activity in skin biopsies as study endpoints. There is increasing awareness by the public of the potential importance of various nutrients, such as wheat bran fiber, vitamins C and E and selenium as well as vitamin A and beta- carotene, in the prevention of cancer. As a result it is becoming more common for people to consume high doses of one or more of these nutrients on a daily basis. It is understood that there may be deleterious interactions between each of these agents when administered in relatively high doses for prolonged periods. We plan to initiate a randomized, double blinded trial to determine whether daily supplementation of the average diet with wheat bran fiber, vitamin E, vitamin C or selenium in relatively high doses will change steady-state plasma, skin and subcutaneous fat concentrations of retinol, retinyl palmitate and/or beta-carotene in 120 normal subjects administered intermediate doses of retinol (25,000 U per day) or beta-carotene (30 mg per day) for up to two years.